1. Field of the Invention
The present invention relates to a novel method for preparing chiral Baclofen, (R)-(+)-β-(Aminomethyl)-4-chlorobenzenepropanoic acid.
2. Description of Related Art
Baclofen is an analog of gamma-aminobutyric acid (GABA) that selectively activates GABAB receptor and is used for treatment of spasticity. It has one chiral center and currently available medicines are of racemic type. It is known that the R-form bears the biological activity. There are many publications about the preparation of R-Baclofen. For example, U.S. Pat. No. 6,051,734 discloses the following scheme:
In this example, racemic 3-(p-chlorophenyl)glutaramide (GAM) is resolved with (S)-(−)-α-methylbenzylamine ((S)-MBA) to form salt of (R)-GAM(S)-MBA which is further converted to (R)-GAM. (R)-GAM is then transformed to (R)-Baclofen via Hoffman rearrangement. The yield from GAM to (R)-GAM is 15.9% (referring to EXAMPLE 2 of U.S. Pat. No. 6,051,734) and yield of Hoffman rearrange is 57.6% (referring to EXAMPLE 4 of U.S. Pat. No. 6,051,734). Overall yield of this process is only 9.2% that rendered this process commercially less competitive.
Accordingly, there is a demand for a simple and more efficient process for preparing (R)-Baclofen with higher yield and lower cost.